Multi-drug resistant bacteria present an increasing problem in US hospitals. To design new antibiotics that are effective against these bacteria, it is important to understand drug-target interactions and the targets themselves. We will study a major antibiotic target: the ribosome. Many ribosome antibiotics interfere with the process of decoding by the ribosome ("tRNA selection"). The rate-limiting step of decoding is accommodation, where the tRNA moves from a partially bound state (A/T state) to its fully bound position (A/A state) inside the ribosome. Structural biology techniques have determined the structure of the ribosome before and after accommodation. Kinetics experiments have determined accommodation rates. It is difficult, however, to study the process of accommodation in atomic detail experimentally. Molecular dynamics simulations have been used to study protein folding. However, until recently, the size of the ribosome has made simulations of ribosome conformational changes computationally prohibitive. We will use large-scale molecular simulation to study key features of accommodation, including the effect of the elongation factor EF-Tu and the effect of antibiotics. We will also combine molecular dynamics diffusion calculations together with measured kinetic rates to estimate accommodation barrier heights that correspond to these measured rates.